UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Its core functions are ubiquitin binding through UBA/SOUBA domains, recognition/sorting of ubiquitinated endosomal cargo into multivesicular bodies, and endosome-specific ESCRT-I complex membership. General ESCRT-I membrane-fission annotations from MVB12A/VPS37B structural work should not be treated as direct UBAP1 evidence.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000813 ESCRT I complex | IBA GO_REF:0000033 | ACCEPT | Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation. Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Component of the ESCRT-I complex file:human/UBAP1/UBAP1-uniprot.txt consists of TSG101, VPS28, VPS37A and UBAP1 PMID:21757351 identify a novel ESCRT-I component PMID:21757351 defines an endosome-specific ESCRT-I complex PMID:22405001 coassembles in a stable 1:1:1:1 complex |
| GO:0043130 ubiquitin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Ubiquitin binding is a core UBAP1 molecular-function annotation. Reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Binds to ubiquitinated cargo proteins file:human/UBAP1/UBAP1-uniprot.txt Interacts (via UBA domains) with ubiquitinated proteins PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 solenoid of overlapping UBAs PMID:22405001 interact with ubiquitin |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IBA GO_REF:0000033 | ACCEPT | Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt sorting of endocytic ubiquitinated cargos PMID:21757351 required for sorting EGFR to the MVB PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 essential for degradation of antiviral cell-surface proteins |
| GO:0000813 ESCRT I complex | IEA GO_REF:0000002 | ACCEPT | Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation. Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Component of the ESCRT-I complex file:human/UBAP1/UBAP1-uniprot.txt consists of TSG101, VPS28, VPS37A and UBAP1 PMID:21757351 identify a novel ESCRT-I component PMID:21757351 defines an endosome-specific ESCRT-I complex PMID:22405001 coassembles in a stable 1:1:1:1 complex |
| GO:0005768 endosome | IEA GO_REF:0000044 | ACCEPT | Summary: endosome localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0005829 cytosol | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: cytosol is supported as a localization context but is not the core functional site. Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Cytoplasm, cytosol |
| GO:0043130 ubiquitin binding | IEA GO_REF:0000002 | ACCEPT | Summary: Ubiquitin binding is a core UBAP1 molecular-function annotation. Reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Binds to ubiquitinated cargo proteins file:human/UBAP1/UBAP1-uniprot.txt Interacts (via UBA domains) with ubiquitinated proteins PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 solenoid of overlapping UBAs PMID:22405001 interact with ubiquitin |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IEA GO_REF:0000002 | ACCEPT | Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt sorting of endocytic ubiquitinated cargos PMID:21757351 required for sorting EGFR to the MVB PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 essential for degradation of antiviral cell-surface proteins |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent UBAP1 function. Reason: The informative molecular function is ubiquitin binding, and the informative component/process terms are ESCRT-I complex and MVB sorting. Proposed replacements: ubiquitin binding ESCRT I complex Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Binds to ubiquitinated cargo proteins file:human/UBAP1/UBAP1-uniprot.txt Interacts (via UBA domains) with ubiquitinated proteins PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 solenoid of overlapping UBAs PMID:22405001 interact with ubiquitin file:human/UBAP1/UBAP1-uniprot.txt Component of the ESCRT-I complex file:human/UBAP1/UBAP1-uniprot.txt consists of TSG101, VPS28, VPS37A and UBAP1 PMID:21757351 identify a novel ESCRT-I component PMID:21757351 defines an endosome-specific ESCRT-I complex PMID:22405001 coassembles in a stable 1:1:1:1 complex |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: cytosol is supported as a localization context but is not the core functional site. Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Cytoplasm, cytosol |
| GO:0000813 ESCRT I complex | IPI PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation. Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Component of the ESCRT-I complex file:human/UBAP1/UBAP1-uniprot.txt consists of TSG101, VPS28, VPS37A and UBAP1 PMID:21757351 identify a novel ESCRT-I component PMID:21757351 defines an endosome-specific ESCRT-I complex PMID:22405001 coassembles in a stable 1:1:1:1 complex |
| GO:0010008 endosome membrane | NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | ACCEPT | Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0036258 multivesicular body assembly | NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | ACCEPT | Summary: multivesicular body assembly is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt sorting of endocytic ubiquitinated cargos PMID:21757351 required for sorting EGFR to the MVB PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 essential for degradation of antiviral cell-surface proteins |
| GO:0043328 protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | ACCEPT | Summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt sorting of endocytic ubiquitinated cargos PMID:21757351 required for sorting EGFR to the MVB PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 essential for degradation of antiviral cell-surface proteins |
| GO:0090148 membrane fission | NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | MARK AS OVER ANNOTATED | Summary: Membrane fission is over-transferred for UBAP1 as written. Reason: The cited structural/autophagy work uses a VPS37B-MVB12A-containing ESCRT-I headpiece and VPS28 mutants, not UBAP1-containing ESCRT-I. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A PMID:32424346 Mutation of VPS28 helical interface residues file:human/UBAP1/UBAP1-uniprot.txt Binds to ubiquitinated cargo proteins file:human/UBAP1/UBAP1-uniprot.txt Interacts (via UBA domains) with ubiquitinated proteins |
| GO:0005768 endosome | EXP PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: endosome localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-184269 | ACCEPT | Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3149434 | ACCEPT | Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917696 | ACCEPT | Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917730 | ACCEPT | Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function. Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Endosome file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Recruited to endosomes as part of the ESCRT-I complex PMID:21757351 endosome-specific ESCRT-I complex |
| GO:0000813 ESCRT I complex | IDA PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation. Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Component of the ESCRT-I complex file:human/UBAP1/UBAP1-uniprot.txt consists of TSG101, VPS28, VPS37A and UBAP1 PMID:21757351 identify a novel ESCRT-I component PMID:21757351 defines an endosome-specific ESCRT-I complex PMID:22405001 coassembles in a stable 1:1:1:1 complex |
| GO:0005829 cytosol | IDA PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | KEEP AS NON CORE | Summary: cytosol is supported as a localization context but is not the core functional site. Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Cytoplasm, cytosol |
| GO:0043130 ubiquitin binding | IDA PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: Ubiquitin binding is a core UBAP1 molecular-function annotation. Reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Binds to ubiquitinated cargo proteins file:human/UBAP1/UBAP1-uniprot.txt Interacts (via UBA domains) with ubiquitinated proteins PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 solenoid of overlapping UBAs PMID:22405001 interact with ubiquitin |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IMP PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt sorting of endocytic ubiquitinated cargos PMID:21757351 required for sorting EGFR to the MVB PMID:21757351 endosomal ubiquitin homeostasis PMID:22405001 essential for degradation of antiviral cell-surface proteins |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | KEEP AS NON CORE | Summary: cytoplasm is supported as a localization context but is not the core functional site. Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. Supporting Evidence: file:human/UBAP1/UBAP1-uniprot.txt Predominantly cytosolic file:human/UBAP1/UBAP1-uniprot.txt Cytoplasm, cytosol |
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Download this section (compressed HTML)Q: Should UBAP1 membrane-fission annotations be removed or kept non-core unless UBAP1-containing ESCRT-I is directly tested in membrane-scission/autophagosome-closure assays?
Suggested experts: GO ESCRT curators, GO autophagy editors
Q: Should generic UBAP1 protein-binding annotations be replaced by ubiquitin binding and ESCRT-I complex membership?
Suggested experts: GO molecular function editors, UniProt curators
Experiment: Compare purified or reconstituted UBAP1-ESCRT-I and MVB12A-ESCRT-I complexes in membrane-remodeling assays and in cell-based autophagosome-closure assays.
Hypothesis: UBAP1-containing ESCRT-I specializes in endosomal ubiquitinated cargo sorting and should not be assumed to provide the same membrane-fission function as MVB12A-containing ESCRT-I without direct evidence.
Type: UBAP1-containing ESCRT-I membrane remodeling assay
Experiment: Rescue UBAP1 knockout cells with wild-type and SOUBA/UBA mutants and measure EGFR/BST2 cargo degradation, endosomal ubiquitin homeostasis, and ESCRT-I recruitment.
Hypothesis: UBAP1 SOUBA/UBA-mediated ubiquitin binding is required for endosomal cargo sorting.
Type: UBAP1 ubiquitin-binding rescue
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